2-Chloro-6,7-dimethoxy-4-quinazolinamine → Doxazosin Monohydrochloride

HRID 1448959Notes

Reaction equation

[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[C:4]([Cl:16])[N:3]=1.[O:17]1[C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=2[O:20][CH2:19][CH:18]1[C:27]([N:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1)=[O:28]>C(O)CCC>[ClH:16].[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[C:4]([N:32]2[CH2:33][CH2:34][N:29]([C:27]([CH:18]3[O:17][C:22]4[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=4[O:20][CH2:19]3)=[O:28])[CH2:30][CH2:31]2)[N:3]=1

Participants

Conditions

Temperature: 80 °C

Procedure

4-Amino-2-chloro-6,7-dimethoxyquinazoline (140 g.) and N-(1,4-benzodioxan-2-carbonyl)piperazine (150 g.) were stirred together under reflux in n-butanol (2 l.) for 31/2 hours. The mixture was then cooled to 80° C., the solid product collected, washed with cold n-butanol (2×250 ml.), and dried. The crude product was dissolved in hot (80° C.) dimethylformamide (530 ml.) and water (130 ml.), filtered, concentrated in vacuo to about 300 ml., then cooled and ether (1.8 l.) added. The solid so obtained was collected and washed with ether to give 4-amino-2-[4-(1,4-benzodioxan-2-carbonyl)piperazin-1-yl]-6,7-dimethoxyquinazoline hydrochloride (215 g.), m.p. 289°-290° C.

Workup

customthe solid product collected
washwashed with cold n-butanol (2×250 ml.)
customdried
dissolutionThe crude product was dissolved in hot (80° C.) dimethylformamide (530 ml.) and water (130 ml.)
filtrationfiltered
concentrationconcentrated in vacuo to about 300 ml
temperature, then cooled
additionether (1.8 l.) added
customThe solid so obtained
customwas collected
washwashed with ether

Sources & evidence

ORD record: ord-4f0648326c2246dc88d983f1058208de
Source dataset: uspto-grants-1980_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04188390

Reaction notes

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